Ma Lei, Chen Yongjun, Han Rui, Wang Shuangyi
Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Traditional Chinese medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Braz J Med Biol Res. 2019 Apr 8;52(4):e8409. doi: 10.1590/1414-431X20198409.
Benzyl isothiocyanate (BITC) has been shown to inhibit invasion and induce apoptosis of various types of cancer. However, its role on human oral squamous cell carcinoma (OSCC) cells is still not well elucidated. In the present study, we investigated the effect of BITC on apoptosis and invasion of SCC9 cells, and its underlying mechanisms in vitro and in vivo. SCC9 cells were exposed to BITC (5 and 25 μM) for 24 and 48 h. Cell growth, apoptosis, invasion, and migration were detected in vitro by MTT, FITC-conjugated annexin V/propidium iodide staining followed by flow cytometry, Matrigel-coated semi-permeable modified Boyden, and wound-healing assay. S100A4, PUMA, and MMP-9 expressions were detected to investigate its mechanisms. Xenotransplantation experiments were used to investigate the role of BITC on tumor growth and lung metastasis. BITC inhibited cell viability and induced cell apoptosis in a dose- and time-dependent manner through upregulation of PUMA signals. BITC inhibited cell invasion and migration by downregulation of S100A4 dependent MMP-9 signals. The ip administration of BITC reduced tumor growth but not lung metastasis of SCC9 cells subcutaneously implanted in nude mice. BITC treatment activated pro-apoptotic PUMA and inhibited S100A4-dependent MMP-9 signals, resulting in the inhibition of cell growth and invasion in cultured and xenografted SCC9 cells. Thereby, BITC is a potential therapeutic approach for OSCC.
异硫氰酸苄酯（BITC）已被证明可抑制多种癌症的侵袭并诱导其凋亡。然而，其在人口腔鳞状细胞癌（OSCC）细胞中的作用仍未得到充分阐明。在本研究中，我们调查了BITC对SCC9细胞凋亡和侵袭的影响及其在体外和体内的潜在机制。将SCC9细胞暴露于BITC（5和25μM）中24和48小时。通过MTT、异硫氰酸荧光素（FITC）偶联的膜联蛋白V/碘化丙啶染色后流式细胞术、基质胶包被的半透性改良博伊登小室以及伤口愈合试验在体外检测细胞生长、凋亡、侵袭和迁移。检测S100A4、p53上调凋亡调节因子（PUMA）和基质金属蛋白酶-9（MMP-9）的表达以研究其机制。采用异种移植实验研究BITC对肿瘤生长和肺转移的作用。BITC通过上调PUMA信号以剂量和时间依赖性方式抑制细胞活力并诱导细胞凋亡。BITC通过下调S100A4依赖性MMP-9信号抑制细胞侵袭和迁移。腹腔注射BITC可降低皮下接种于裸鼠的SCC9细胞的肿瘤生长，但不影响肺转移。BITC处理激活促凋亡的PUMA并抑制S100A4依赖性MMP-9信号，从而抑制培养的和异种移植的SCC9细胞的生长和侵袭。因此，BITC是一种潜在的OSCC治疗方法。
